ES2753356T3 - A procedure and device for determining a patient's body fluid glucose level, and a computer program product - Google Patents

Abstract

A method for determining a body fluid glucose level of a patient from a continuous signal from a glucose sensing element of a body fluid continuous glucose monitoring device in a data processing unit, comprising: - receiving measurement data representing a continuous sensor signal provided by a glucose sensing element of a body fluid continuous glucose monitoring device in the data processing unit, - receiving calibration data representing a zero signal level dependent on the time of the glucose sensing element in the data processing unit, - determining a level of glucose in body fluid by processing at least the measurement data and the calibration data in the data processing unit, the processing comprising the subtraction of the level time-dependent zero signal signal from continuous sensor signal, and - provide res data Results indicative of the continuous glucose level in body fluid in the processing unit, characterized in that receiving the calibration data comprises receiving calibration data representing a time-dependent zero signal level comprising time-dependent interfering signal contributions representing a presence of an interfering substance in the body fluid for which the glucose level in the body fluid is determined, wherein the interfering substance is a substance other than glucose and the sensing element is sensitive to the interfering substance in the body fluid.

Description

DESCRIPTION

A procedure and device for determining a patient's body fluid glucose level, and a computer program product

The present disclosure relates to a method and system for determining a patient's body fluid glucose level, and a computer program product.

Background

Medical devices are often used as diagnostic devices and / or therapeutic devices to diagnose and / or treat medical conditions of patients. For example, a blood glucose meter is used as a diagnostic device to measure the blood glucose levels of patients with diabetes. An insulin infusion pump is used as a therapeutic device to administer insulin to patients with diabetes.

Diabetes mellitus, often called diabetes, is a chronic condition in which a person has elevated glucose levels that result in defects in the body's ability to produce and / or use insulin. There are three main types of diabetes. Type 1 diabetes can be autoimmune, genetic, and / or environmental and usually affects children and young adults. Type 2 diabetes accounts for 90 to 95% of diabetes cases and is linked to obesity and physical inactivity. Gestational diabetes is a form of glucose intolerance diagnosed during pregnancy and usually disappears spontaneously after delivery.

Diabetes is mainly treated by controlling blood glucose. This level is dynamic and complex, and is affected by multiple factors, including the amount and type of food consumed, and the amount of insulin (which mediates the transport of glucose through cell membranes) in the blood. Glucose levels are also sensitive to exercise, sleep, stress, smoking, travel, illness, menstruation, and other unique psychological and lifestyle factors for individual patients. The dynamic nature of blood glucose and insulin, and all other factors that affect blood glucose, often require a person with diabetes to predict blood glucose levels. Therefore, treatment in the form of insulin or oral medications, or both, can be scheduled to keep blood glucose levels in an appropriate range.

Managing diabetes is often time consuming for patients due to the need to constantly obtain reliable diagnostic information, follow prescribed treatment, and monitor lifestyle on a daily basis. Diagnostic information, such as blood glucose, is typically obtained from a capillary blood sample with a lancing device and then measured with a portable blood glucose meter. Interstitial glucose levels can be obtained from a continuous glucose sensor that is worn in the body.

A portable device can receive patient information from several different sources, such as an insulin pump, a continuous glucose monitor, a computer program, user input, etc. To use this information accurately, the portable device may have to calibrate the information received from these sources. For example, a portable diabetes monitoring device can receive raw data from a continuous glucose monitor that is related to a patient's glucose level. To make use of these raw data, the portable diabetes monitoring device may have to be calibrated to correlate the raw data received with a measured blood glucose level from the patient. The accuracy of this calibration can affect patient care and treatment. Accordingly, there is a need for a method of calibrating a portable diabetes monitoring device to determine an exact estimated glucose level from a patient from data received from a continuous glucose monitor.

A variety of implantable electrochemical sensors have been proposed to detect specific analytes or compositions in a patient's blood. For example, glucose sensors are provided for use in obtaining an indication of blood glucose levels in a patient. Such readings are useful for monitoring a treatment that typically includes regular insulin administration. The sensor signals provided by the sensor device are processed to determine the actual glucose level. In EP 1 154 718 B1 the use of a regression is proposed to correlate the sensor signals representing the measurement data with the actual blood glucose level.

US 6,326,160 B1 discloses procedures, systems and devices for measuring the concentration of a target analyte presented in a biological system using a series of measurements obtained from a monitoring system and an Mixture of Experts (MOE) algorithm. of Experts "). A method of measuring blood glucose in a subject is disclosed.

WO 2012/084157 A1 relates to a method for calibrating a portable diabetes monitoring device based on data generated by a continuous glucose monitor. The method may include sampling a continuous glucose monitor stream at a sampling interval over a period of time to generate a plurality of current samples for the period of time. The procedure may also include determining a mean, median, and standard deviation of the plurality of current samples. The level of The patient's blood glucose can be measured for the first time and a calibration equation associating the plurality of current samples with the patient's estimated glucose level based on the measured blood glucose level and the plurality of current samples can be determined when the standard deviation is less than a first threshold and an absolute value of a difference between the mean and the median is less than a second threshold.

Document US 2012/0191362 A1 discloses a method for operating measurement equipment to detect an analyte in body fluid by means of a continuous measurement blood glucose sensor. A calibration procedure is performed for prospective calibration of the measurement equipment. At least three calibration points are detected in the calibration procedure, where each calibration point comprises a measurement signal from the measuring equipment and a reference value of an associated reference measurement. A plurality of possible slopes is established between the calibration points. In at least one robust estimation procedure, a formation of at least one median is used to determine a probable slope from the plurality of possible slopes. In addition, a measurement is carried out. During measurement and use of the probable slope, a concentration of the analyte in the body fluid is deduced from a measurement signal from the measuring equipment and the probable slope.

US 2007/0038053 A1 discloses a procedure for continuously measuring the concentration of target chemical analytes present in a biological system, and processing specific analyte signals to obtain a measurement value that is highly correlated with the concentration of the target chemical analyte in the biological system. A raw measurement signal is processed in a conversion stage to remove or correct the background information present in the signal. One of those bottom signals is the benchmark fund. The reference fund interferes with the measurement of the analyte of interest. The reference fund may vary over time. Furthermore, electrochemically active interfering species and / or residual analytes may be present in the device, which will further interfere with the measurement of the analyte of interest.

Drug interference has been considered to potentially mask a serious condition in the glucose level of a body fluid (Tang et al .: "Effects of Drugs on Glucose Measurements with handheld glucose meters and a portable glucose analyzer", Clinical Chemistry, 2000; 113, pages 75-86).

US 2013/0338628 A1 refers to a system that includes a processor and at least one memory configured to provide a response determinant. The response determinant can receive therapeutic and wellness data. Furthermore, the response determinant can determine a response based on the therapeutic and wellness data received. The response may represent a reaction to a substance integrated with an ingestion event marker. The determined response can be provided, for example, to a treatment controller.

US 2013/0297222 A1 discloses procedures and apparatus that allow an analyte concentration to be estimated from a measurement in the presence of compounds that interfere with the measurement.

US 2012/0191362 A1 discloses a method for operating measurement equipment to detect an analyte in body fluid by means of a continuous measurement blood glucose sensor. A calibration procedure is performed for prospective calibration of the measurement equipment.

US 2014/0138261 A1 refers to procedures and systems for applying a plurality of test voltages to the test strip and measuring an emitted transient current resulting from an electrochemical reaction in a test chamber of the test strip so that it can be determining an estimated interference value so that the interference value can be used to correct transients at specific time points for a more accurate determination of glucose concentration.

US 2010/0292932 A1 refers to a method and apparatus for estimating the characteristics of target materials using kinetic change information over time, by measuring the result of a chemical reaction between two materials, target materials and reactant. , with an optical or electrochemical procedure.

Summary

It is an objective to provide a method and a system that provides the determination of a body fluid glucose level of a patient from a continuous signal from a glucose sensor element of a continuous body fluid glucose monitoring device in a manner effective and reliable.

A method and system for determining a body fluid glucose level of a patient is provided according to claims 1 and 7, respectively. Furthermore, a computer program product according to claim 8 is provided. Advantageous advances are disclosed in the dependent claims.

According to one aspect, a method is provided for determining a patient's body fluid glucose level from a continuous signal from a glucose sensor element of a body fluid continuous glucose monitoring device in a processing unit. of data. In the processing unit Data Measurement data is received, the measurement data representing a continuous sensor signal provided by a glucose sensor element of a body fluid continuous glucose monitoring device in the data processing unit. The glucose sensor element can be configured for subcutaneous access, for example, a measurement in the gap. Furthermore, calibration data is received in the data processing unit, the calibration data representing a time-dependent zero signal level of the glucose sensing element. A glucose level of a body fluid is determined by processing at least the measurement data and the calibration data in the data processing unit. In the processing step, the calibration data representing the time-dependent zero signal level is subtracted from the continuous signal from the sensor. Results data indicative of body fluid glucose level are provided to the processing unit, which may be independent of an additional blood glucose reference.

In accordance with another aspect, a system is provided for determining a patient's body fluid glucose level from a continuous signal from a glucose sensing element of a body fluid continuous glucose monitoring device. The system comprising a data processing unit configured to receive measurement data representing a continuous sensor signal provided by a glucose sensor element of a continuous glucose monitoring device in body fluid, receives calibration data representing a level time dependent zero signal signal of the glucose sensing element, determines a continuous glucose level of a body fluid by processing at least the measurement data and the calibration data in the data processing unit, the processing comprising subtracting the level of time dependent zero signal of the sensor continuous signal, and provides result data indicative of the continuous glucose level of the body fluid in the processing unit.

The glucose signal element zero signal level that is different from a zero result (a result that is a zero signal, not detectable) is indicative of a contribution from the sensor output signal in response to a substance other than glucose in body fluid under investigation.

The body fluid under investigation may be, for example, one of interstitial fluid, blood, and urea.

Receiving the calibration data comprises receiving calibration data representing a zero signal level comprising an interfering signal contribution indicative of the presence of at least one interfering substance in the body fluid for which the glucose level is determined. The glucose sensing element responds to the presence of the interfering substance (interfering substance) in the body fluid under investigation. In conclusion, with respect to the electrical output signal of the glucose sensor element there is a signal interference that affects the zero signal level.

The interfering signal contribution is a time dependent interfering signal contribution. Alternatively, the interfering signal contribution may not be time dependent, which may also be referred to as constant interfering signal contribution.

Receiving the calibration data may comprise receiving calibration data representing a decomposition kinetic cycle of an interfering substance in the body fluid for which the glucose level is determined. The decomposition kinetic cycle may represent an (additional) interfering signal contribution with respect to its time dependency and / or its time dependent signal height expected at the output of the glucose sensing element.

Receiving the calibration data may comprise receiving an event start input indicative of a start time of the presence of the interfering substance in the body fluid for which the glucose level is determined. Together with the kinetic decomposition cycle of the interfering substance, this information can be used to calibrate the sensor signals received from the glucose sensor element.

In the procedure for determining the glucose level, receiving the calibration data may comprise generating a warning signal for the input of calibration data. By means of the warning signal, the user can be asked to provide the entry of the calibration data.

Generating the warning signal may comprise receiving a user select input. For example, the user may select to input calibration data from some external or internal storage media.

The processing unit may be provided in one of a portable body fluid glucose monitoring device and a continuous body fluid glucose measurement device. In some embodiments, the processing unit may be provided in one of a portable blood glucose monitoring device, a continuous blood glucose measuring device, a portable interstitial fluid monitoring device, and a blood glucose measuring device. glucose continues in interstitial fluid.

With respect to the system for determining the glucose level of a patient's body fluid, the embodiments described above with reference to the method can be applied accordingly.

In accordance with another aspect, not necessarily to be combined with the procedure or system for determining the glucose level in a patient's body fluid, a method for determining a pharmacokinetic curve for an active substance or composition in a body fluid can be provided to from a continuous signal from the sensor of a glucose sensor element of a continuous glucose monitoring device in body fluid in a data processing unit. In the processing unit, first measurement data is received, with the first measurement data representing a continuous sensor signal provided by a glucose sensor element of a continuous glucose monitoring device in body fluid. The glucose sensor element can be configured for subcutaneous access. The glucose sensor element can be configured to measure interstitial fluid or blood. In the data processing unit, additional data is provided, eg, second measurement data, the additional data representing a sensor signal provided from additional body fluid glucose monitoring different from the continuous glucose monitoring device in body fluid. Additional body fluid glucose monitoring may also be of the continuous body fluid glucose monitoring type. The first measurement data and additional data are processed to determine a pharmacokinetic curve of an active substance or composition that causes time-dependent signal interference for the first measurement data. The additional data is not interfered with by the signal contribution of the active substance. Therefore, a pharmacokinetic curve can be determined from the processing of the first measurement data and additional data. If the first measurement data and additional data represent the same glucose level of a patient, but are measured independently, the pharmacokinetic curve can be determined by simply subtracting the additional data from the first measurement data. Surprisingly, measurements to determine the level of glucose in body fluid can be used to determine the kinetic behavior of an active substance or composition in body fluid.

In general, the procedure can also be performed using measured data from a sensor element that provides signals indicative of another analyte, such as lactate, present in the body fluid under investigation. Body fluid may be, for example, one of interstitial fluid, blood, and urea. It is necessary to analyze at least two independent data sources (for example, measurement with the active component present and measurement without the presence of the active component). One or more steps of the procedure can be combined with the procedure or system to determine a patient's body fluid glucose level provided in the present disclosure. One or more steps of the procedure or system for determining the level of glucose in a patient's body fluid can also be combined with the procedure for determining a pharmacokinetic curve for an active substance or composition in body fluid.

The data used in the method of determining the pharmacokinetic curve of an active substance or composition in a body fluid from the continuous signal from the sensor of the glucose sensor element of the continuous glucose monitoring device in body fluid, at least in part, they can be taken from a calibration procedure performed for the device. Different calibration procedures can be applied, for example, comparing calibration with constant displacement and calibration with calibrated displacement.

Description of embodiments

Embodiments are described below, by way of example, with reference to the figures. In the figures they show:

fig. 1 a schematic representation of a patient and a doctor in charge,

fig. 2 a schematic representation of a patient with a continuous glucose monitor (GMC), a permanent ambulatory insulin infusion pump, a non-permanent ambulatory insulin infusion pump and a diabetes controller,

fig. 3 a schematic representation of a diabetes treatment system,

fig. 4 a functional block diagram of a diabetes controller,

fig. 5 a functional block diagram of a continuous glucose body fluid,

fig. 6 a block diagram of a procedure for determining a patient's body fluid glucose level from continuously measured sensor signals from a glucose sensor element, and

fig. 7 graphical representation of time-dependent curves and

fig. 8 a block diagram of a procedure for determining a patient's body fluid glucose level from continuously measured sensor signals from a glucose sensor element.

Referring now to fig. 1, a 100 person with diabetes and a healthcare professional 101 are shown in a clinical setting. People with diabetes include people with metabolic syndrome, prediabetes, type 1 diabetics, type 2 diabetics and gestational diabetics and are jointly called patients. Diabetes healthcare professionals are diverse and include nurses, medical nurses, physicians, and endocrinologists, and are jointly referred to as physicians.

During a health consultation, patient 100 typically shares with physician 101 a variety of data including blood glucose measurements, continuous glucose monitor data, amounts of insulin infused, amounts of food and beverages consumed, exercise schedules, and other information about Lifestyle. Physician 101 may obtain additional patient data including measurements of HbA1C, cholesterol, triglyceride, blood pressure, and patient weight 100. Patient data can be recorded manually or electronically on a diabetes monitoring device laptop 102, a diabetes analysis software run on a personal computer (PC) 106 and / or a diabetes analysis website (not shown). Physician 101 may analyze patient data manually or electronically using the diabetes analysis software and / or the diabetes analysis website. After analyzing patient data and reviewing patient 100 adherence to previously prescribed treatment, practitioner 101 can decide whether to modify treatment for patient 100.

Referring now to fig. 2, patient 100 may use a continuous glucose monitor (GMC) 200, a permanent ambulatory insulin infusion pump 201 or a non-permanent ambulatory insulin infusion pump 202 (together, insulin pump 201 or 202), and the portable diabetes monitoring device 102 (hereinafter the diabetes manager 102). The GMC 200 uses a subcutaneous sensor to detect and monitor the amount of glucose in the subcutaneous fluid of patient 100 and reports the corresponding readings to the portable diabetes control device 102.

Diabetes Controller 102 performs various tasks, including measuring and recording blood glucose levels, determining an amount of insulin to be delivered to patient 100 using insulin pump 201 or 202, receiving patient data through an interface user, archive patient data, etc. Diabetes Controller 102 periodically receives readings from GMC 200 indicating a level of glucose in subcutaneous fluid from patient 100. Diabetes Controller 102 transmits instructions to insulin pump 201 or 202, which supplies insulin to patient 100. Insulin can be delivered in the form of a rapid dose, which increases the amount of insulin in patient 100's blood by a predetermined amount. Additionally, insulin can be delivered on a scheduled basis in the form of a basal dose, which maintains a predetermined level of insulin in the patient's blood 100.

Referring now to fig. 3, a diabetes monitoring system 300 used by patient 100 and physician 101 includes one or more of the following devices: diabetes manager 102, continuous glucose monitor (GMC) 200, insulin pump 201 or 202, a mobile device 301, the diabetes analysis software on PC 103, and other healthcare devices 302. Diabetes controller 102 is configured as a central system and communicates with devices in the control system diabetes 300. Alternatively, insulin pump 202 or mobile device 301 can serve as the central system. Communication between the various devices in the diabetes control system 300 can be accomplished using wireless interfaces (eg, Bluetooth) and / or wired interfaces (eg, USB). The communication protocols used by these devices may include protocols that comply with the IEEe 11073 standard that are extended using the guidelines provided by the Continua.RTM Health Alliance Design Guidelines. In addition, health care record systems like Microsoft.RTM. HealthVault.TM. and Google.TM. Health can be used by patient 100 and physician 101 to exchange information.

The diabetes controller 102 may receive glucose readings from one or more sources (eg, from the GMC 200). The GMC 200 continuously measures the glucose level of patient 100. The GMC 200 periodically communicates the glucose level to the diabetes controller 102. The diabetes controller 102 and the GMC 200 communicate wirelessly using a proprietary wireless protocol.

Additionally, the Diabetes Controller 102 includes a blood glucose meter (GM) and a port that communicates with the GM (both not shown). The port can receive a blood glucose test strip 303. Patient 100 deposits a sample of blood or other body fluid on the blood glucose test strip 303. The GM analyzes the sample and measures the blood glucose level in the shows. The blood glucose level measured from the sample and / or the blood glucose read by the GMC 200 can be used to determine the amount of insulin to be administered to the patient 100.

Diabetes controller 102 communicates with insulin pump 201 or 202. Insulin pump 201 or 202 can be configured to receive instructions from diabetes controller 102 to deliver a predetermined amount of insulin to patient 100. Additionally, the Insulin pump 201 or 202 may receive other information including meal and / or exercise schedules from patient 100. Insulin pump 201 or 202 can determine the amount of insulin to deliver based on the additional information.

Insulin pump 201 or 202 can also communicate data to diabetes controller 102. The data may include amounts of insulin delivered to patient 100, corresponding delivery times, and status of bomb. Diabetes controller 102 and insulin pump 201 or 202 can communicate using a wireless communication protocol such as Bluetooth. Other wired or wireless communication protocols can also be used.

Furthermore, the diabetes controller 102 can communicate with other healthcare devices 302. For example, the other healthcare devices 302 may include a sphygmomanometer, a scale, a pedometer, a pulsed pulse oximeter, a thermometer, etc. The other healthcare devices 302 obtain and communicate personal health information from the patient 100 to the diabetes controller 102 through wireless, USB or other interfaces. The other 302 healthcare devices use communication protocols that comply with ISO / IEEE 11073 extended using the Continual.RTM guidelines. Health Alliance. Diabetes controller 102 can communicate with the other healthcare devices 302 using interfaces including Bluetooth, USB, etc. Furthermore, the devices of the diabetes monitoring system 300 can communicate with each other via the diabetes controller 102.

Diabetes Controller 102 can communicate with PC 103 using Bluetooth, USB or other interfaces. A diabetes control software program running on PC 103 includes an analyzer-configurator that stores configuration information for devices of the diabetes control system 300. The configurator has a database to store configuration information for the diabetes controller 102 and other devices. The configurator can communicate with users through standard web or computer screens in non-web applications. The configurator transmits user-approved configurations to the diabetes control system 300 devices. The analyzer retrieves data from the diabetes controller 102, stores the data in a database, and generates analysis results through standard web pages or computer screens in non-web based applications.

Diabetes controller 102 can communicate with mobile device 301 using Bluetooth. Mobile device 301 can include a mobile phone, a PDA, or a pager. Diabetes controller 102 can send messages to an external network through mobile device 301. Mobile device 301 can transmit messages to the external network based on requests received from diabetes controller 102.

In some embodiments, the GMC 200 measures the level of glucose in the interstitial fluid of patient 100 by sampling a stream. The glucose level in the interstitial fluid, and thus the sampled current, is related to the glucose level of patient 100. To accurately estimate the glucose level of patient 100 based on the glucose level in the interstitial fluid As measured by the GMC 200, the Diabetes Controller 102 can be periodically calibrated.

Diabetes Controller 102 can be calibrated by determining a calibration equation based on at least one current sample and at least one blood glucose measurement. It can be assumed that the current sampled by GMC 200 and the blood glucose level of patient 100 have a linear relationship within a normal measurement region of approximately 40 to 400 milligrams per deciliter. Based on this assumed linear relationship, the calibration equation can be a linear equation that associates one or more current samples with an estimated glucose level from the patient. After calibration, the diabetes controller 102 can determine an estimated glucose level from patient 100 based on the calibration equation and the current sampled by the GMC 200.

Referring now to fig. 4, an example of a diabetes controller 102 includes a blood glucose (GM) measurement module 400, a communication module 401, a user interface module 402, user interfaces 403, a processing module 404, memory 405 and a power supply module 406. User interface module 402 and processing module 404 can be implemented by an application processing module 407. The GM 400 module includes a blood glucose measurement instrument that analyzes samples provided by the patient. 100 on the blood glucose test strip 303 and which measures the amount of blood glucose in the samples. Communication module 401 can include multiple radios that communicate with different devices of diabetes control system 300. User interface module 402 connects diabetes controller 102 to various user interfaces 403 that patient 100 can use to interface with diabetes controller 102. For example, user interfaces 403 may include keys, switches, a display, a speaker, a microphone, a secure digital card (SD) port, and / or a USB port (all not shown).

Processing module 404 processes the data received from GM module 400, communication module 401, and user interface module 402. Processing module 404 uses memory 405 to process and store data. Memory 405 can include volatile and nonvolatile memory. The processing module 404 outputs data to and receives data from user interfaces 403 via user interface module 402. Processing module 404 outputs data to and receives data from devices of the diabetes control system 300 via the communication module 401. Power module 406 supplies power to components of diabetes controller 102. Power module 406 may include a rechargeable battery or other power source. The battery can be recharged, for example, using an adapter that plugs into a power outlet and / or via a USB port on the diabetes 102 controller.

Referring now to fig. 5, an example of a continuous glucose monitor (GMC) 200 includes a sensor 500, a communication module 501, a processing module 502, memory 503, and a power module 504. Sensor 500 can monitor a condition of patient 100 that it is related to the glucose level of the patient 100. For example, the sensor 500, alone or in combination with the processing module 502, may periodically sample a current value that corresponds to the glucose level in the interstitial fluid of the patient 100 The communication module 501 may include one or more radios that communicate with different devices of the diabetes control system 300.

Processing module 502 processes the data received from sensor 500 and communication module 501. Processing module 502 uses memory 503 to process and store data. Memory 503 can include volatile and nonvolatile memory. Processing module 502 outputs data to and receives data from devices (eg, diabetes controller 102) of diabetes control system 300 via communication module 501. Power module 504 supplies power to the components of the GMC 200. In some embodiments, the power module 504 includes a battery or other power source. The power source may include a battery that can be recharged, for example, using an adapter that plugs into an electrical outlet.

Referring to fig. 6, an example of procedure 600 is illustrated for determining a continuous glucose level in a patient's body fluid. Procedure 600 begins at step 601, where measurement data is received at a data processing unit. The data processing unit, for example, can be provided on the portable diabetes monitoring device 102 or the continuous glucose monitor 200. The processing module 404 or 502 can be provided with the data processing unit. . The received measurement data is indicative of a continuous sensor signal provided by a glucose sensor element such as sensor 500.

In step 602, the calibration data is received at the data processing unit, the calibration data representing a time-dependent zero signal level of the glucose sensor element used to detect the continuous signal from the sensor. The zero signal level of the glucose sensor element is different from a zero result (a result that is actually a zero signal, not detectable) and may be indicative of a contribution from the sensor output signal in response to one or more active substances other than glucose in the body fluid (blood) under investigation. In step 603, the continuous blood glucose level is determined by processing at least the measurement data and the calibration data in the data processing unit, said processing comprising the subtraction of the zero signal level from the continuous sensor signal provided by glucose sensing element. The contributions of the sensor signal caused by any substance other than glucose are removed thereafter. Such signal processing can be considered as (part of) a calibration.

The calibration data may represent a zero signal level comprising an interfering signal contribution indicative of the presence of at least one interfering substance in the body fluid for which the glucose level is determined. For example, the patient may have taken acetylsalicylic acid, the time-dependent decomposition of which may cause the contribution of the time-dependent sensor signal. Information on the time dependence of decomposition of acetylsalicylic acid, for example, can be obtained from C. Bogentoft, et al .: Influence of Food on the Absorption of Acetylsalicylic Acid from Enteric-Coated Dosage Forms, Europ. J. clin. Pharmacol. 14, 351-355 (1978).

The glucose sensing element responds to the presence of the interfering substance (interfering substance) in the body fluid under investigation, for example blood or interstitial fluid. In conclusion, with respect to the electrical output signal of the glucose sensor element there is a signal interference that affects the zero signal level.

For the purpose of further explanation, FIGS. 7a to 7d show time dependent signal curves derived from a simulation. Referring to fig. 7a, a continuous time-dependent sensor signal is shown representing a signal from a glucose sensor, eg, a current signal, for which signal interference was initiated at a time of 2800 min. The simulated temporal dependence of the interfering signal is shown in fig. 7b.

In fig. 7c, curve A represents a continuous, uncorrected glucose level derived from the signal curve of the sensor of FIG. 7a. Curve B represents the corrected continuous glucose level derived from subtracting the interfering signal. Finally, fig. 7d shows the difference between curve A and B in fig. 7c. Said curve represents a pharmacokinetic cycle of the interfering composition in the body fluid under investigation. Within the noise level of the sensor element by which the signals are detected, fig. 7d resembles the curve in fig. 7b.

Referring to fig. 8, an example of method 800 is illustrated for determining a pharmacokinetic curve for an active substance or composition in a body fluid from a continuous signal from the sensor of a glucose sensor element of a continuous glucose monitoring device in body fluid in a data processing unit. Procedure 800 begins at step 801 where measurement data is received in the processing unit first, the first measurement data representing a continuous sensor signal provided by a glucose sensor element of a glucose monitoring device continues in body fluid. The glucose sensor element can be configured for subcutaneous access. The data processing unit, for example, can be provided on the portable diabetes monitoring device 102 or the continuous glucose monitor 200. The processing module 404 or 502 can be provided with the data processing unit. . The received measurement data is indicative of a continuous sensor signal provided by a glucose sensor element such as sensor 500.

In step 802, in the data processing unit, second measurement data is provided, the second measurement data representing a sensor signal provided from additional body fluid glucose monitoring different from the continuous glucose monitoring device in body fluid. Additional body fluid glucose monitoring may also be of the continuous body fluid glucose monitoring type. The first and second measurement data are processed to determine a pharmacokinetic curve of an active substance or composition that causes time-dependent signal interference for the first measurement data. The second measurement data is not interfered with by the signal contribution of the active substance. Therefore, a pharmacokinetic curve can be determined from the processing of the first and second measurement data (step 803). If the first and second measurement data represent the same glucose level of a patient, but are measured independently, the pharmacokinetic curve can be determined by simply subtracting the second measurement data from the first measurement data. Surprisingly, measurements to determine the level of glucose in body fluid can be used to determine the kinetic behavior of an active substance or composition in body fluid.

In general, procedure 800 can also be performed using measured data from a sensor element that provides signals indicative of another analyte, such as lactate, present in the body fluid under investigation. Body fluid can be different from blood, for example urea or interstitial fluid. It is necessary to analyze at least two independent measurements (measurement with the active component present; measurement without the presence of the active component). One or more steps of procedure 800 can be combined with procedure 600 or the system to determine a patient's body fluid glucose level provided in the present disclosure. One or more steps of procedure 600 or the system for determining a patient's body fluid glucose level may also be combined with procedure 800 for determining the pharmacokinetic curve for an active substance or composition in body fluid.

Claims (8)

A method of determining a patient's body fluid glucose level from a continuous signal from a glucose sensor element of a continuous body fluid glucose monitoring device in a data processing unit, comprising: - receiving measurement data representing a continuous sensor signal provided by a glucose sensor element from a continuous body fluid glucose monitoring device in the data processing unit, - receiving calibration data representing a time-dependent zero signal level from the glucose sensor element in the data processing unit, - determining a level of glucose in body fluid by processing at least the measurement data and the calibration data in the data processing unit, the processing comprising the subtraction of the time-dependent zero signal level of the continuous signal from the sensor, and - providing result data indicative of the level of continuous glucose in body fluid in the processing unit, characterized in that receiving the calibration data comprises receiving calibration data representing a time-dependent zero signal level comprising time-dependent interfering signal contributions representing a presence of an interfering substance in body fluid for which the glucose level in body fluid, where the interfering substance is a different substance from glucose and the sensing element is sensitive to the interfering substance in the body fluid. The method according to claim 1, wherein receiving the calibration data comprises receiving calibration data representing a kinetic cycle of decomposition of an interfering substance in the body fluid for which the level of glucose in body fluid is determined . The method according to claim 1 or 2, wherein receiving the calibration data comprises receiving an event start input indicative of a start time of the presence of the interfering substance in the body fluid for which it is determined. the level of glucose in body fluid. Method according to one of the preceding claims, in which receiving the calibration data comprises generating a warning signal for the input of calibration data. The method according to claim 4, wherein generating the warning signal comprises receiving a user selection input. Method according to one of the preceding claims, wherein the processing unit is provided in one of a portable body fluid glucose monitoring device and a continuous body fluid glucose measurement device. 7. A system for determining a patient's body fluid glucose level from a continuous signal from a glucose sensor element of a body fluid continuous glucose monitoring device, the system comprising a data processing unit, configured for: - receiving measurement data representing a continuous sensor signal provided by a glucose sensor element from a continuous glucose monitoring device in body fluid, - receiving calibration data representing a time-dependent zero signal level from the glucose sensor element, - determining a level of glucose in body fluid by processing at least the measurement data and the calibration data in the data processing unit, the processing comprising the subtraction of the time-dependent zero signal level of the continuous signal from the sensor, and - providing result data indicative of the level of glucose in body fluid in the processing unit, characterized in that receiving the calibration data comprises receiving calibration data representing a time-dependent zero signal level comprising contributions of interfered-with signal dependent on the time representing a presence of an interfering substance in the body fluid for which the level of glucose in body fluid is determined, in which the interfering substance is a different substance from glucose and the sensor element is sensitive to the interfering substance in the body fluid. 8. A computer program product for determining a patient's body fluid glucose level from a continuous signal from a glucose sensor element of a body fluid continuous glucose monitoring device in a data processing unit, which includes: - means recorded on an electronic data medium for receiving measurement data representing a continuous sensor signal provided by a glucose sensor element of a continuous body fluid glucose monitoring device in the data processing unit, - means registered on the electronic data carrier for receiving calibration data representing a time-dependent zero signal level of the glucose sensor element in the data processing unit, - means recorded on the electronic data carrier for determining a level of glucose in body fluid by processing at least the measurement data and the calibration data in the data processing unit, the processing comprising the subtraction of the zero signal level dependent on the continuous signal time from the sensor, and - means recorded on the electronic data medium to provide result data indicative of the level of continuous glucose in body fluid in the processing unit, characterized in that receiving the calibration data comprises receiving calibration data representing a time-dependent zero signal level comprising time-dependent interfering signal contributions representing a presence of an interfering substance in body fluid for which the glucose level in body fluid, where the interfering substance is a different substance from glucose and the sensing element is sensitive to the interfering substance in the body fluid.